Journal of neurotrauma
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Journal of neurotrauma · Jun 2018
Poor Motor-Function Recovery after Spinal Cord Injury in Anxiety-Model Mice with Phospholipase C-Related Catalytically Inactive Protein Type 1 Knockout.
Mice with a knockout of phospholipase C (PLC)-related inactive protein type 1 (PRIP1-/- mice) display anxiety-like behavior and altered γ-aminobutyric acid (GABA)A-receptor pharmacology. Here, we examined associations between anxiety and motor-function recovery in PRIP1-/- mice after a spinal cord injury (SCI) induced by a moderate contusion injury at the 10th thoracic level. Uninjured PRIP1-/- mice showed less distance than wild-type (WT) mice in the center 25% in an open field test (OFT), indicating anxiety-like behavior. ⋯ In PRIP1-/- mice after SCI, the percentage of distance spent in the center 25% of the OFT was correlated with the OFT distance traveled and with the latency to fall in the rotarod test. Six weeks after SCI, ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) expressions were elevated at the lesion epicenter in PRIP1-/- mice, and spinal cord atrophy and demyelination were more severe than in WT mice. The axonal fiber development was also decreased in PRIP1-/- mice, consistent with the poor motor-function recovery after SCI in these mice.
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Journal of neurotrauma · Jun 2018
Chloroquine Promotes the Recovery of Acute Spinal Cord Injury by Inhibiting Autophagy-Associated Inflammation and Endoplasmic Reticulum Stress.
Spinal cord injury (SCI) is a severe nervous system disease that may lead to lifelong disability. Studies have shown that autophagy plays a key role in various diseases; however, the mechanisms regulating cross-talk between autophagy, inflammation, and endoplasmic reticulum (ER) stress during SCI recovery remain unclear. This study was designed to investigate the mechanism by which chloroquine (CQ) inhibits autophagy-associated inflammation and ER stress in rats during their recovery from acute SCI. ⋯ Overexpression of p62 increases I-κBα degradation and improves inflammatory responses. Moreover, CQ treatment also inhibits the activation of ER stress in the rat SCI model, and the ATF4 signaling pathway is required for ER-stress-induced activation of autophagy. These findings reveal a novel mechanism underlying the beneficial effects of CQ on the recovery of SCI, particularly the mechanisms regulating cross-talk between autophagy, inflammation, and ER stress.
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Journal of neurotrauma · Jun 2018
Effects of Treadmill Training Combined with Serotonergic Interventions on Spasticity after Contusive Spinal Cord Injury.
Spasticity usually emerges during the course of recovery from spinal cord injury (SCI). While medications and physical rehabilitation are prescribed to alleviate spastic symptoms, the insufficiency of their effects remains an important problem to be addressed. Given the challenges associated with increasing the dose of medication, we hypothesized that a combination therapy with medication and physical rehabilitation can be effective. ⋯ Moreover, TMT suppressed the expression of the 5-HT2A receptor in the lumbar spinal motor neurons, while cyproheptadine treatment did not change it. We did not observe any differences in locomotor functions between the groups. Taken together, our findings indicate that TMT and cyproheptadine significantly alleviated spastic symptoms, but did not show synergistic or additive effects.
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Journal of neurotrauma · Jun 2018
Partial Recovery of Proprioception in Rats with Dorsal Root Injury after Human Olfactory Bulb Cell Transplantation.
Transplanted human olfactory ensheathing cells (hOECs) were mixed with collagen into a unilateral transection of four dorsal roots (C6-T1) in a rat model. By mixing with collagen, the limited numbers of hOEC were maximized from an olfactory bulb biopsy and optimize cavity filling. Cyclosporine was administered daily to prevent immune rejection. ⋯ Responder and nonresponder rats were compared with regard to microglial activation within the deep dorsal horn of cervical levels C7, C8 and also axon loss within the cuneate fasciculus at cervical level C3. Little difference was seen in microglial activation or axonal loss that could account for the improved proprioception in the responders group. This preliminary study is the first to transplant human olfactory bulb cells into a rat model of dorsal root injury; by refining each component part of the procedure, the repair potential of OECs can be maximized in a clinical setting.
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Journal of neurotrauma · Jun 2018
Diffusion Tensor Imaging of Scarring, Necrosis, and Cavitation Based on Histopathological Findings in Dogs with Chronic Spinal Cord Injury: Evaluation of Multiple Diffusion Parameters and Their Correlations with Histopathological Findings.
The use of diffusion tensor imaging (DTI) for the characterization of various lesion types in dogs with spinal cord injury (SCI) has not been investigated. The aim of this study was to characterize scarring (loose immature scarring [LIMS], intermediate mature scarring [IMS], and dense mature scarring [DMS]), necrosis, cavitation, and acute hemorrhage using multiple DTI parameters and determine the correlations between the DTI parameters and histopathological finding in dogs with controlled SCI. All imaging data were obtained from the lumbar spinal cord (from L1 to L3) of normal and SCI dogs using a 3-Tesla magnetic resonance imaging scanner. ⋯ The maturation grade of scarring demonstrated a positive linear correlation with fractional anisotropy and the planar index and a negative linear correlation with the spherical index and the radial, mean, and axial diffusivities. These results suggest the feasibility of using DTI for detailed noninvasive monitoring of SCI. DTI can provide critical information for guiding therapeutic strategies and determining the prognosis of SCI patients.